A Study of Nivolumab + Chemotherapy or Nivolumab + Ipilimumab Versus Chemotherapy in Non-Small Cell Lung Cancer (NSCLC) Participants With Epidermal Growth Factor Receptor (EGFR) Mutation Who Failed 1L or 2L EGFR Tyrosine Kinase Inhibitor (TKI) Therapy
- Conditions
- Non-Small-Cell Lung Carcinoma
- Interventions
- Registration Number
- NCT02864251
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The main purpose of this study is to determine whether nivolumab + chemotherapy is effective as compared to chemotherapy in the treatment of patients with EGFR mutation, NSCLC who failed first line (1L) or second-line (2L) EGFR TKI therapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 367
- Confirmed stage IV or recurrent EGFR mutated NSCLC with disease progression on one or two prior lines of treatment with EGFR TKIs (allowed TKIs must be approved by the local health authority, including but not limited to erlotinib, gefitinib, afatinib, dacomitinib and osimertinib). In osimertinib treated subjects, T790 testing is not required.
- No evidence of exon 20 T790M mutation obtained at progression on prior first- or second-generation EGFR TKI therapy. For participants who were treated with osimertinib, T790M testing is not required.
- Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
- Available tumor sample for Programmed death-ligand 1 (PD-L1) immunohistochemical (IHC).
- Participants are eligible if central nervous system (CNS) metastases are considered to be adequately controlled/treated before or during the screening period and participants are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to randomization. In addition, participants must be either off corticosteroids, or on a stable or decreasing dose of ≤10 mg daily prednisone (or equivalent) for at least 2 weeks prior to randomization). Participants with asymptomatic CNS metastasis are eligible.
- Eastern Cooperative Group (ECOG) Performance Status 0-1
- Life expectancy is at least 3 months
- Known EGFR mutation, T790M positive who failed 1L first- or second-generation TKI should receive osimertinib first as the standard of care (SOC). These participants are only eligible if they fail osimertinib as 2L.
- who have progressed within 3 months of the first dose of 1L or 2L EGFR TKI.
- Carcinomatous meningitis
- Active, known or suspected autoimmune disease are excluded
- ALK translocation
- Known SCLC transformation
- Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
Other protocol defined inclusion/exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Nivolumab+Platinum doublet chemotherapy Nivolumab - Nivolumab+Platinum doublet chemotherapy Cisplatin - Nivolumab + Ipilimumab Nivolumab Enrollment is closed for this arm Nivolumab + Ipilimumab Ipilimumab Enrollment is closed for this arm Platinum doublet chemotherapy Cisplatin - Nivolumab+Platinum doublet chemotherapy Carboplatin - Nivolumab+Platinum doublet chemotherapy Pemetrexed - Platinum doublet chemotherapy Pemetrexed - Platinum doublet chemotherapy Carboplatin -
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) by Blinded Independent Centralized Review (BICR) From randomization to the date of first documented tumor progression or death (approximately 58 months) PFS is defined as the time between the date of randomization and the date of first documented tumor progression, as determined by BICR (per RECIST v1.1 criteria), or death due to any cause, whichever occurs first.
Participants who died without reported progression will be considered to have progressed on the date of their death. Subsequent therapy was accounted for by censoring at the last evaluable tumor assessment on or prior to the date of subsequent therapy.
Progression is the appearance of one or more new lesions. RECIST - "response evaluation criteria in solid tumors" is a standard system to measure tumor response to treatment.
Based on Kaplan-Meier estimates
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) by Blinded Independent Centralized Review (BICR) From randomization to the date of first documented disease progression or death due to any cause (approximately 67 months) DOR is the time between the date of first response (CR or PR) and the date of first documented disease progression as determined by Response Evaluation Criteria In Solid Tumors (RECIST 1.1) or death due to any cause (death occurring after re-treatment or randomization to new combination treatment was not included), whichever occurred first.
PR is at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as reference. CR is disappearance of all target lesions and a reduction in the short axis of pathological lymph nodes to \<10 mm (whether target or non-target).
Radiographic tumor response assessments from Week 7 (± 7 days), then every 6 weeks (± 7 days) until Week 49 and every 12 weeks (± 7 days) thereafter, until disease progression, treatment discontinued, or the start of subsequent anti-cancer therapy.
Participants who neither progress nor die were censored on the date of their last assessment.
Median computed using Kaplan-Meier method12 Month Progression Free Survival Rates (PFSR) by Blinded Independent Centralized Review (BICR) 12 Months after first treatment dose The PFSR at 12 months is defined as the percent of treated participants remaining progression free and surviving at 12 months since the first dosing date. Progression is the appearance of one or more new lesions. Point estimates are derived from Kaplan-Meier analyses.
9 Month Progression Free Survival Rates (PFSR) by Blinded Independent Centralized Review (BICR) 9 months after first treatment dose The PFSR at 9 months is defined as the percent of treated participants remaining progression free and surviving at 9 months since the first dosing date. Progression is the appearance of one or more new lesions.
Point estimates are derived from Kaplan-Meier analyses.Overall Survival (OS) From randomization to the date of death due to any cause (up to approximately 67 months) Overall Survival (OS) is defined as the time between the date of randomization and the date of death due to any cause. OS will be censored on the last date a participant was known to be alive.
Median based on Kaplan-Meier EstimatesObjective Response Rate (ORR) by Blinded Independent Centralized Review (BICR) From randomization to the date of objectively documented progression, date of death, or the date of subsequent therapy (up to approximately 67 months) ORR is number of randomized participants who have confirmed best overall response (BOR) of complete response (CR) or partial response (PR) using RECIST v1.1 criteria by BICR assessment.
BOR is the best response designation, between randomization and objectively documented progression per RECIST v1.1 criteria by BICR or the date of subsequent anti-cancer therapy, whichever occurs first.
PR is at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as reference. CR is disappearance of all target lesions and a reduction in the short axis of pathological lymph nodes to \<10 mm (whether target or non-target).
Radiographic tumor response assessments from Week 7 (± 7 days), then every 6 weeks (± 7 days) until Week 49 and every 12 weeks (± 7 days) thereafter, until disease progression, treatment discontinued, or the start of subsequent anti-cancer therapy.
CR+PR, confidence interval based on the Clopper and Pearson method.
Trial Locations
- Locations (51)
Local Institution - 0033
🇺🇸Los Angeles, California, United States
Torrance Memorial Physican Network
🇺🇸Redondo Beach, California, United States
Baylor Scott and White Research Institute
🇺🇸Temple, Texas, United States
Pacific Shores Medical Group
🇺🇸Long Beach, California, United States
Texas Health Physicians Group
🇺🇸Arlington, Texas, United States
Local Institution - 0019
🇨🇳Kaohsiung, Taiwan
Local Institution - 0037
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Local Institution - 0029
🇺🇸Los Angeles, California, United States
Local Institution - 0061
🇺🇸Orange, California, United States
Local Institution - 0004
🇺🇸Chicago, Illinois, United States
Local Institution - 0003
🇺🇸New Haven, Connecticut, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Local Institution - 0002
🇺🇸Boston, Massachusetts, United States
Local Institution - 0064
🇺🇸New York, New York, United States
Duke University Medical Center
🇺🇸Butner, North Carolina, United States
Local Institution - 0063
🇺🇸Tyler, Texas, United States
Local Institution - 0168
🇨🇦Montreal, Quebec, Canada
Local Institution - 0001
🇺🇸Salt Lake City, Utah, United States
Local Institution
🇨🇳Taoyuan, Taiwan
Local Institution - 0166
🇨🇦Edmonton, Alberta, Canada
Local Institution - 0043
🇨🇳Changsha, Hunan, China
Local Institution - 0017
🇨🇳Hangzhou, Zhejiang, China
Local Institution - 0024
🇭🇰Hong Kong, Hong Kong
Local Institution - 0156
🇫🇷Paris, France
Local Institution - 0016
🇨🇳Hangzhou, Zhejiang, China
Local Institution - 0059
🇯🇵Kurume, Fukuoka, Japan
Local Institution - 0070
🇯🇵Sapporo, Hokkaido, Japan
Local Institution - 0097
🇯🇵Itami, Hyogo, Japan
Local Institution - 0076
🇯🇵Hidaka, Saitama, Japan
Local Institution - 0078
🇯🇵Koto-ku, Tokyo, Japan
Local Institution - 0077
🇯🇵Sendai-shi, Miyagi, Japan
Local Institution - 0069
🇯🇵Chuo, Tokyo, Japan
Local Institution - 0058
🇯🇵Osakasayama, Osaka, Japan
Local Institution - 0081
🇯🇵Yokohama-shi, Kanagawa, Japan
Local Institution - 0079
🇯🇵Tokyo, Japan
Local Institution - 0038
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Local Institution - 0035
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Local Institution - 0041
🇸🇬Singapore, Singapore
Local Institution - 0036
🇰🇷Gyeonggi-do, Korea, Republic of
Local Institution - 0042
🇸🇬Singapore, Singapore
Local Institution - 0021
🇨🇳Tainan, TNN, Taiwan
Local Institution - 0158
🇪🇸Barcelona, Spain
Local Institution - 0018
🇨🇳Taichung, Taiwan
Local Institution - 0045
🇨🇳Chiayi, Taiwan
Local Institution - 0066
🇨🇳Taipei, Taiwan
Local Institution - 0023
🇨🇳Taipei, Taiwan
Local Institution - 0108
🇨🇳Taipei, Taiwan
Local Institution - 0027
🇭🇰Hong Kong, Hong Kong